We will investigate the mechanisms of endothelial injury in several connective tissue diseases that involve the lung. Studies will be performed with cultured pulmonary endothelial cells and with experimental animals to determine the mechanisms of immune injury in scleroderma, systemic lupus erythematosus, rheumatoid arthritis (RA) and Felty's syndrome (FS). Other disorders, such as Wegener's granulomatosus or Goodpasture's syndrome will also be investigated. The models for immune injury will include: immune complexes, leukocyte- and complement-mediated injury, antibody-dependent cytotoxicity and cell-mediated cytotoxicity. Specifically, the role of immune complexes in neutropenia and defective neutrophil function of Felty's syndrome, rheumatoid arthritis and SLE will be investigated by determining whether phagocytosis of immune complexes causes adherence of neutrophils to endothelium, whether intermediate complexes mediate these phenomena, and whether contact between endothelium and neutrophils depends upon Fc or C3b receptors. The role of cell-mediated cytotoxicity in diseases such as scleroderma will be explored. The presence of IgG on neutrophils from patients with FS, RA and SLE will be detected by immunofluorescence techniques, and the relationship of antibody to endothelial damage will be determined. Cytotoxic effects of patients' sera on pulmonary endothelial cells will be studied. Antibody-mediated immune complex-mediated or lymphoid cell dependent antibody-mediated cytotoxicity (ADCC) directed at the endothelial cell will be investigated. Release of 51Cr and specific endothelial cell markers (e.g., factor VIII antigen and angiotensin I converting enzyme) will be used as an indication of endothelial cell injury. The sensitivity of pulmonary endothelial cells to these immune injuries will be compared with the sensitivity of endothelial cells from other vascular beds, and the influence of immune injury on the rate of cell replication will be determined.